The Food and Drug Administration (FDA) recently published a draft guidance that outlines the “Naming of Drug Products Containing Salt Drug Substances” in accordance with the recently implemented USP Salt Policy, which became effective on May 1, 2013. The USP Salt Policy, applies to “all new drug product monographs for products that contain an active ingredient that is a salt.” It should be noted that the guidance only applies to prescription drug products approved under the FD&C Act, and does not apply to nonprescription drugs or to biological products licensed under the Public Health Service Act.
The naming changes are noted on the following mock label:
The FDA states that “the policy will make it easier for health care practitioners to calculate an equivalent dose when transferring patients from one dosage form to another (e.g., calculating dose from an injection to a tablet), even if both the products contain active ingredients that are different salts, because the strengths and names both will be based on the active moiety.” The benefits of this policy are demonstrated by Erythromycin. A common antibiotic, Erythromycin is available in a wide variety of salts and dosage forms. Erythromycin Lactobionate is sold as injectable, while Erythromycin Stearate is sold as an oral tablet. Having a conversion between the dose of Erythromycin and of the dose of each salt form would be imperative for a pharmacist or clinician to prescribe/administer the appropriate dose when changing dosage and/or salt forms.
While the Erythromycin example displays the advantages of this policy, there are a handful of instances where this policy may be more harmful than helpful, and these exceptions are described in the guidance. Overall, the FDA summarizes their exception policy to apply to any case where “the name of the salt conveys vital information from a clinical perspective.” These exceptions include:
Simple Salts: If the “active ingredient is a relatively simple salt and administration of the entire salt is therapeutically important” the full name would be maintained. Examples include: potassium chloride, lithium carbonate, and calcium gluconate.
Electrolyte Intake: If “clinically significant amounts of cations…accompany the active moiety of a drug product” the full name would be maintained. “Clinical significance may be related to the recommended maximum daily amount of an electrolyte intake in special patient populations. Examples include: recommended daily intake of sodium in patients with congestive heart failure or recommended daily intake of potassium in patients with chronic kidney disease.”
Differing Pharmacokinetics: If there is scientific evidence which shows that the salt form of a product affects pharmacokinetic parameters “in a manner that influences the clinician’s product selection” the full name would be maintained.
Adverse Events: If there is a “significant evidence-based safety concern that the counter-ion part of the salt could cause acid-base disturbances, hepatic, renal or other organ damage, or hypersensitivity reactions,” the full name would be maintained.
Continuity:If the “name of the salt is necessary to maintain consistency with other dosage forms of the same active ingredient (salt)” the full name would be maintained. “For example, if a tablet dosage form that was approved before May 1, 2013, included the salt in its established name and the drug product’s strength is based on the salt form, the naming convention would not change for a new capsule dosage form, the naming convention would not change for a new capsule dosage form with the same active ingredient (salt) that is approved after the effective date.”
Safety Concerns: If “there are relevant, documented safety reasons (e.g., documented medication errors related to name or strength) in a closely related product” the full name would be maintained.
Though this guidance applies only to new drug products, the FDA states that if there are relevant safety concerns discovered post-approval, the name can be retrospectively changed. Similarly, while USP won’t be changing the current existing monographs, and therefore this rule will only be applied going forward, it is possible that a past monograph may be changed if safety or historical reasons deem this necessary. The guidance mentions that the FDA’s Center for Drug Evaluation and Research (CDER) and the USP have agreed to work together in order to minimize confusion in the event of “any retrospective name changes.”
The FDA places the responsibility on the drug sponsor to consider whether this policy will apply to them and whether or not an exception is reasonable. The drug sponsor must then compile data and a rationale in order to present this information to CDER for feedback. The Weinberg Group specializes in developing regulatory strategies for drug sponsors and can assist in applying the recommendations in this and other FDA guidances.
Posted by Emily Krulewitz, Researcher. For more information, please contact Emily at firstname.lastname@example.org.